Gut Microbes Transform Bile Acid Molecules by a Flip

Being human is worthwhile but our tiny friends couldn't allow you to be one. Previously, scientists said that cells that make us constitute only about 43% of the human body, and the microbes fill up the rest. Researchers have now identified one more set of microbial genes that are involved in the conversion of bile acids to other forms, whose characteristics are yet to be recognized.

Researchers from the University of Illinois identified a set of new genes that convert bile acids to some other forms, which can either be beneficial or harmful. Two genes in this range were already identified while evidence from past research was used to trace the remaining set of genes.

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‘Clostridium paraputrificum produces reductases that flip a specific hydroxyl group present on carbon-12 in bile acid molecules. The human gut microbiome is found to produce the same by an exclusive set of genes.’

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"Locating these bacterial genes will allow mechanistic studies to determine the effect of bile acid conversion on host health. If we find this is a beneficial reaction, therapeutic strategies can be developed to encourage the production of these bile acids in the gastrointestinal tract," says lead author Jason Ridlon, Associate professor in the Department of Animal Sciences at U of I.

A flip by Clostridium paraputrificum

Bile acids are produced by the liver to help us digest fats and fat-soluble vitamins in the diet. Microbes at the end of our small intestine convert bile acids into other forms like deoxycholic acid (DCA) and lithocholic acid (LCA) which can either be beneficial or harmful. They do so by using enzymes that can turn over three hydroxyl groups on bile acid molecules.

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Having identified genes that produce two of these enzymes, researchers from the University of Illinois used existing literature to arrive at a strategy in finding the last one. Clostridium paraputrificum is known to produce reductases that flip a specific hydroxyl group present on carbon-12 in bile acid molecules.

Thus, scientists identified all the genes that produced it, engineered them into E. coli, and looked for ones that can do the same. While the results from this experiment were applied to the human microbiome, it was found that many bacteria have genes with that particular bile acid metabolizing function.

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Can’t judge ‘good or bad’

Our knowledge about the gut microbiome has improved but, it is still not clear whether this kind of bile acid conversion through the flip of the hydroxyl group at carbon-12 is of any advantage for therapeutic applications.

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Ridlon notes that "good vs. bad" framing oversimplifies reality because on one side lower levels of DCA and LCA seems to match up with infection by Clostridium difficile whereas, on the other hand, excess accumulation of DCA and LCA through diet can damage DNA and cause cancers of the colon, liver, and esophagus.

Thus, Ridlon concludes, "A major goal of this research is trying to establish and maintain a 'Goldilocks zone' of bile acids - not too much or too little."

The study reveals some new insights into gut microbiome research. Further investigations about the end products of bile acid conversions will unravel links between the characteristics of the gut microbiome and the development of diseases.

Source-Medindia